Abstract
For over four decades, the principal target of antifungal therapy has been the fungal cell membrane sterol ergosterol. Although this has proven to be a successful and relatively selective antifungal target, collateral toxicity to mammalian cells (amphotericin B) and drug interactions (azoles) have been by-products of agents that target the fungal cell membrane. In the 1970s, the echinocandins were identified during the screening of fungal fermentation products for new antibiotic agents. These agents were subsequently shown to inhibit production of β(1,3)-glucan, a key structural component of the fungal cell wall. Subsequent chemical modification of these natural products has led to the development of safer, semi-synthetic β(1,3)-glucan synthase inhibitors with enhanced microbiological and clinical efficacy against infections caused by Candida and Aspergillus species. In this review, the pharmacology, spectrum and clinical efficacy of the three leading β(1,3)-glucan synthase inhibitors (caspofungin, micafungin and anidulafungin), which have completed phase III clinical trials, will be discussed and a perspective for the role of these agents in the management of life-threatening mycoses will be offered.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1313-1327 |
| Number of pages | 15 |
| Journal | Expert Opinion on Investigational Drugs |
| Volume | 12 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 1 2003 |
| Externally published | Yes |
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Keywords
- Anidulafungin
- Aspergillus
- Candida
- Caspofungin
- Micafungin
ASJC Scopus subject areas
- Pharmacology
Cite this
The echinocandin antifungals : An overview of the pharmacology, spectrum and clinical efficacy. / Wiederhold, Nathan; Lewis, Russell E.
In: Expert Opinion on Investigational Drugs, Vol. 12, No. 8, 01.08.2003, p. 1313-1327.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The echinocandin antifungals
T2 - An overview of the pharmacology, spectrum and clinical efficacy
AU - Wiederhold, Nathan
AU - Lewis, Russell E.
PY - 2003/8/1
Y1 - 2003/8/1
N2 - For over four decades, the principal target of antifungal therapy has been the fungal cell membrane sterol ergosterol. Although this has proven to be a successful and relatively selective antifungal target, collateral toxicity to mammalian cells (amphotericin B) and drug interactions (azoles) have been by-products of agents that target the fungal cell membrane. In the 1970s, the echinocandins were identified during the screening of fungal fermentation products for new antibiotic agents. These agents were subsequently shown to inhibit production of β(1,3)-glucan, a key structural component of the fungal cell wall. Subsequent chemical modification of these natural products has led to the development of safer, semi-synthetic β(1,3)-glucan synthase inhibitors with enhanced microbiological and clinical efficacy against infections caused by Candida and Aspergillus species. In this review, the pharmacology, spectrum and clinical efficacy of the three leading β(1,3)-glucan synthase inhibitors (caspofungin, micafungin and anidulafungin), which have completed phase III clinical trials, will be discussed and a perspective for the role of these agents in the management of life-threatening mycoses will be offered.
AB - For over four decades, the principal target of antifungal therapy has been the fungal cell membrane sterol ergosterol. Although this has proven to be a successful and relatively selective antifungal target, collateral toxicity to mammalian cells (amphotericin B) and drug interactions (azoles) have been by-products of agents that target the fungal cell membrane. In the 1970s, the echinocandins were identified during the screening of fungal fermentation products for new antibiotic agents. These agents were subsequently shown to inhibit production of β(1,3)-glucan, a key structural component of the fungal cell wall. Subsequent chemical modification of these natural products has led to the development of safer, semi-synthetic β(1,3)-glucan synthase inhibitors with enhanced microbiological and clinical efficacy against infections caused by Candida and Aspergillus species. In this review, the pharmacology, spectrum and clinical efficacy of the three leading β(1,3)-glucan synthase inhibitors (caspofungin, micafungin and anidulafungin), which have completed phase III clinical trials, will be discussed and a perspective for the role of these agents in the management of life-threatening mycoses will be offered.
KW - Anidulafungin
KW - Aspergillus
KW - Candida
KW - Caspofungin
KW - Micafungin
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UR - http://www.scopus.com/inward/citedby.url?scp=0042134553&partnerID=8YFLogxK
U2 - 10.1517/13543784.12.8.1313
DO - 10.1517/13543784.12.8.1313
M3 - Article
C2 - 12882619
AN - SCOPUS:0042134553
VL - 12
SP - 1313
EP - 1327
JO - Current Opinion in Investigational Drugs
JF - Current Opinion in Investigational Drugs
SN - 1354-3784
IS - 8
ER -